發(fā)布時間：2018-04-19 13:33

  本文選題：動脈粥樣硬化 + ATRA��； 參考：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：目的探討全反式維甲酸(all-trans-retinoic acid,ATRA)對實驗性動脈粥樣硬化兔動脈血管內(nèi)皮舒張功能的影響及其機制。方法普通級新西蘭大耳白兔隨機分3組,正常組:飼喂普通飼料;模型組:飼喂高脂飼料(普通飼料+1%膽固醇+5%豬油);ATRA組:飼喂高脂飼料,同時ATRA灌胃5 mg/(kg·d)。8周后,麻醉處死,頸動脈取血,檢測血脂濃度。動脈大體油紅染色觀察斑塊形成情況。HE染色觀察動脈內(nèi)皮結(jié)構(gòu)變化。高分辨率血管超聲檢測內(nèi)皮舒張功能。離體動脈環(huán)實驗檢測ATRA對動脈內(nèi)皮舒張功能的影響。免疫組織化學實驗檢測MLCK在動脈血管的表達情況。Western blot檢測動脈MLCK及MAPK信號通路相關(guān)蛋白的表達情況。結(jié)果高脂飲食8周后,模型組動脈粥樣硬化形成,ATRA灌胃后,對動脈粥樣硬化的發(fā)生有抑制作用。與正常組相比,模型組血清中三酰甘油(TG)、總膽固醇(TCH)、高密度脂蛋白-膽固醇(HDL-c)、低密度脂蛋白-膽固醇(LDL-c)濃度明顯升高(P0.05);油紅染色表明脂質(zhì)斑塊明顯;HE染色顯示血管內(nèi)膜增厚,泡沫細胞增多,平滑肌細胞極性紊亂,向內(nèi)膜遷移;離體動脈環(huán)實驗和高分辨率血管超聲實驗表明內(nèi)皮依賴性舒張功能顯著低于正常組(P0.05);MLCK及MAPK信號通路相關(guān)蛋白(P38,JNK,ERK)表達水平顯著升高(P0.05)。與模型組相比,ATRA組血清中TG,HDL-c,LDL-c濃度無差異,TCH濃度顯著降低(P0.05);油紅染色可見脂質(zhì)斑塊;HE染色可見血管內(nèi)膜稍微增厚,泡沫細胞減少,平滑肌細胞排列較整齊;內(nèi)皮依賴性舒張功能明顯提高(P0.05);MLCK及MAPK信號通路相關(guān)蛋白(P38,JNK,ERK)表達水平顯著下降(P0.05)結(jié)論高脂飲食可使動脈粥樣硬化發(fā)生,動脈內(nèi)皮損傷,動脈內(nèi)皮損傷使血管內(nèi)皮舒張功能下降,ATRA可降低血清中總膽固醇濃度。ATRA改善動脈粥樣硬化內(nèi)皮依賴性舒張功能,其機制可能與MAPK信號通路抑制動脈MLCK的表達有關(guān)。
[Abstract]:Objective to investigate the effect of all-trans-retinoic acid ATRAA on endothelium diastolic function and its mechanism in experimental atherosclerotic rabbits.Methods New Zealand white rabbits were randomly divided into three groups: normal group: normal group: fed normal diet, model group: fed high fat diet (1% cholesterol 5% lard) group: fed high fat diet, and ATRA was fed intragastric for 5 mg/(kg for 8 weeks.Blood was taken from carotid artery and blood lipid concentration was measured.Arterial gross oil red staining was used to observe the plaque formation. He staining was used to observe the changes of arterial endothelial structure.Endothelial diastolic function was measured by high resolution ultrasound.The effect of ATRA on endothelium diastolic function was detected by isolated arterial ring experiment.Immunohistochemistry was used to detect the expression of MLCK in arterial vessels. Western blot was used to detect the expression of MLCK and MAPK signal transduction related proteins.Results after 8 weeks of high fat diet, the formation of atherosclerosis in model group was inhibited by ATRA.Compared with the normal group, the serum levels of TGG, TCHG, HDL-cC, LDL-cc in the model group were significantly higher than those in the normal group, and the oil red staining showed that the lipid plaque was obviously stained with HE to show the thickening of the vascular intima.Foam cells increased, smooth muscle cells polarity disorder, migration to the intima;The results of isolated arterial ring test and high resolution vascular ultrasound showed that the endothelium-dependent diastolic function was significantly lower than that in the normal control group (P 0.05 MLCK and MAPK signal pathway related protein P38 JNKN ERK) expression was significantly higher than that in the control group (P 0.05).Compared with the model group, there was no significant difference in serum TGN HDL-cU LDL-c concentration between the ATRA group and the model group. The concentration of tch decreased significantly in the serum of ATRA group, and the lipid plaque was stained with oil red, the intima was slightly thicker, the foam cells were decreased, and the smooth muscle cells were arranged neatly.Endothelium-dependent diastolic function significantly increased the expression of P0.05MLCK and MAPK signaling pathway related protein P38-JNK-ERK (P 0.05). Conclusion High fat diet can induce atherosclerosis and injury of arterial endothelium.Vascular endothelial diastolic function decreased after arterial endothelial injury. ATRA could decrease serum total cholesterol concentration. ATRA could improve endothelium-dependent diastolic function of atherosclerotic rats. The mechanism may be related to the inhibition of MLCK expression by MAPK signaling pathway.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R543.5

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本文編號：1773299